Citanest Plain

Dosage for prilocaine is highly individualized and must be determined by a qualified healthcare professional. The dose depends on the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, and the patient's physical status.

• For Dental Procedures: The usual dose for a healthy adult is typically between 40 mg and 400 mg (1 to 5 cartridges of a 4% solution). The maximum recommended dose for a healthy adult is generally 8.0 mg/kg of body weight, not to exceed a total of 600 mg within a 2-hour period.
• For Infiltration or Peripheral Nerve Blocks: Doses typically range from 100 mg to 400 mg, depending on the specific nerve being targeted.
• For Topical Application (EMLA): Usually, 1 to 2.5 grams of cream is applied per 10 square centimeters of skin and covered with an occlusive dressing for at least 60 minutes.

Prilocaine must be used with extreme caution in children due to the increased risk of methemoglobinemia.

• Dental Use: For children under 10 years of age, the dose is calculated based on weight and age. Generally, the dose should not exceed 6.6 mg/kg (3.0 mg/lb).
• Topical Use: In infants and children, the maximum dose and application area are strictly limited by weight to prevent systemic toxicity. For example, in infants weighing 3-10 kg, the maximum application area is 10 cm² and the maximum duration is 4 hours.
• Note: Prilocaine is generally avoided in infants under 6 months of age who have not yet reached full metabolic maturity of the enzyme systems that process methemoglobin.

Renal Impairment

Because prilocaine and its metabolites are excreted by the kidneys, patients with severe renal disease may require lower doses or increased monitoring. The accumulation of metabolites in these patients can increase the risk of systemic toxicity and methemoglobinemia.

Hepatic Impairment

Since the liver is a primary site of metabolism for amide local anesthetics, patients with significant liver disease (e.g., cirrhosis or hepatitis) are at a higher risk of developing toxic plasma concentrations. Healthcare providers typically reduce the dose and monitor these patients closely for signs of Central Nervous System (CNS) toxicity.

Elderly Patients

Elderly patients often have reduced physiological reserves, including decreased cardiac output and reduced hepatic/renal blood flow. Consequently, lower doses are often recommended for patients over 65 to avoid toxicity. The dose should be titrated slowly to the desired effect.

Prilocaine is administered by healthcare professionals in a clinical or dental setting.

• Injections: The provider will first aspirate (pull back on the syringe) to ensure the needle is not inside a blood vessel. The injection is then performed slowly to minimize tissue distension and systemic absorption.
• Topical Cream: If you are applying prilocaine/lidocaine cream at home before a procedure, follow your doctor's instructions exactly. Apply the prescribed amount, cover it with the provided dressing, and do not leave it on longer than directed. Wash your hands immediately after application.
• Storage: Injectable prilocaine should be stored at room temperature (20°C to 25°C or 68°F to 77°F) and protected from light. Do not use the solution if it is discolored or contains particles.

Because prilocaine is typically administered as a single dose for a specific procedure by a healthcare provider, missed doses are not common. If you are using a topical formulation and forget to apply it at the scheduled time before a procedure, contact your doctor's office immediately to see if the procedure needs to be rescheduled.

An overdose of prilocaine can lead to Local Anesthetic Systemic Toxicity (LAST). Symptoms may include:

• CNS Signs: Numbness of the tongue, lightheadedness, blurred vision, tremors, and in severe cases, generalized convulsions (seizures).
• Cardiovascular Signs: Low blood pressure (hypotension), slow heart rate (bradycardia), or even cardiac arrest.
• Methemoglobinemia Signs: Bluish coloring of the skin (cyanosis), shortness of breath, and fatigue.

Emergency Measures: If an overdose is suspected, the administration of the drug is stopped immediately. Healthcare providers will ensure the patient has an open airway, provide oxygen, and may administer medications like benzodiazepines for seizures or lipid emulsion therapy to 'soak up' the excess anesthetic from the blood.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose or apply more topical cream than prescribed without medical guidance.

Most side effects of prilocaine are localized and temporary, resolving as the medication wears off. Common experiences include:

• Local Numbness and Tingling: This is the intended effect but may feel strange or uncomfortable as it spreads or fades. It typically feels like a 'pins and needles' sensation (paresthesia).
• Swelling or Redness: Minor inflammation at the site of injection is common and usually subsides within 24 hours.
• Bruising: Small bruises may occur where the needle entered the tissue.
• Pale Skin: Because prilocaine can cause mild vasoconstriction (narrowing of blood vessels), the area may appear paler than the surrounding skin.

• Dizziness: Some patients may feel lightheaded shortly after the injection, often due to a mild systemic absorption or a vasovagal response (fainting reflex) to the needle.
• Nausea: Mild stomach upset may occur, particularly if the patient is anxious about the procedure.
• Tinnitus: A ringing or buzzing in the ears can occur if the drug levels in the blood rise slightly above the normal range.
• Metallic Taste: A brief metallic taste in the mouth is a known sign of early systemic absorption.

• Severe Allergic Reactions: While rare with amide anesthetics, some individuals may experience hives, itching, or swelling of the face and throat.
• Nerve Damage: Prolonged numbness or permanent nerve injury is extremely rare but can occur if the needle causes physical trauma to a nerve or if the drug is injected directly into a nerve bundle.
• Methemoglobinemia: While a specific risk of prilocaine, it remains rare at standard dental doses in healthy adults. However, it is more common in patients with underlying conditions or those receiving very high doses.

> Warning: Stop using Prilocaine (if topical) and call your doctor immediately or seek emergency care if you experience any of these:

1. 1Cyanosis: A bluish or slate-gray discoloration of the lips, skin, or fingernail beds. This is a hallmark sign of methemoglobinemia, indicating that your blood is not carrying enough oxygen.
2. 2Shortness of Breath (Dyspnea): Difficulty breathing or rapid breathing, which may occur even while resting.
3. 3Seizures: Any involuntary shaking, muscle twitching, or loss of consciousness.
4. 4Arrhythmias: A feeling that your heart is skipping beats, racing, or beating too slowly.
5. 5Profound Hypotension: Feeling like you are going to pass out, severe weakness, or actual fainting.
6. 6Anaphylaxis: Sudden difficulty breathing, swelling of the tongue or throat, and a rapid drop in blood pressure.

Prilocaine is generally intended for short-term use. There are no documented 'long-term' side effects from a single clinical use. However, repeated high-dose exposure over a short period could theoretically lead to persistent methemoglobinemia or cumulative toxicity. In very rare cases, if a nerve is injured during the injection, long-term paresthesia (numbness or tingling) in that specific area may persist for weeks or months.

No FDA black box warnings for Prilocaine. However, the FDA does require prominent warnings regarding the risk of Methemoglobinemia. This warning emphasizes that prilocaine can cause this life-threatening condition, especially in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, congenital methemoglobinemia, or those taking other oxidizing drugs. Healthcare providers are instructed to monitor patients for signs of cyanosis and to have methylene blue (the antidote) readily available if high doses are used.

Report any unusual symptoms to your healthcare provider. If you notice persistent numbness that does not go away after several hours, contact your dentist or doctor to ensure no nerve irritation has occurred.

Prilocaine is a powerful medication that must be used with caution. Before receiving prilocaine, it is vital to inform your healthcare provider of your full medical history, including any history of heart disease, liver disease, or blood disorders. Because prilocaine can affect the central nervous system and the heart, it is administered in settings where emergency resuscitation equipment is available. Patients should remain under observation until the initial effects of the anesthesia have begun to subside.

No FDA black box warnings for Prilocaine. While it lacks a black box, the clinical warnings regarding methemoglobinemia are treated with equivalent seriousness in the medical community.

Methemoglobinemia Risk

This is the most significant specific risk associated with prilocaine. The metabolite o-toluidine can reduce the oxygen-carrying capacity of the blood. This risk is highest in:

• Infants under 6 months of age.
• Patients with G6PD deficiency.
• Patients with existing heart or lung disease.
• Patients taking other medications that cause oxidative stress.

Central Nervous System (CNS) Toxicity

If prilocaine is accidentally injected into a blood vessel or if the dose is too high, it can cross the blood-brain barrier. This can cause a progression of symptoms: first, talkativeness and apprehension, then tremors, and finally, generalized seizures. Healthcare providers monitor for these 'pre-seizure' signs to intervene early.

Cardiovascular Risks

Local anesthetics can depress the heart's ability to conduct electrical signals. In high concentrations, prilocaine can cause bradycardia (slow heart rate), heart block, and even cardiac arrest. Patients with pre-existing heart blocks or arrhythmias require extreme caution.

Allergic Reactions

While rare, some prilocaine formulations contain preservatives like methylparaben or sulfites (if epinephrine is included). Patients with known 'sulfite sensitivity' (common in some people with asthma) must inform their doctor, as this can cause life-threatening anaphylaxis.

For routine dental procedures, formal lab monitoring is rarely required. However, for major nerve blocks or high-dose applications, providers may monitor:

• Pulse Oximetry: Note that standard pulse oximeters may give false readings in the presence of methemoglobinemia.
• Blood Pressure and Heart Rate: Monitored during and after the procedure.
• Mental Status: Observed for signs of CNS toxicity.
• Methemoglobin Levels: If cyanosis is observed, a co-oximetry blood test is performed to measure the exact percentage of methemoglobin.

You should not drive or operate heavy machinery until the effects of prilocaine have completely worn off and you feel fully alert. Local anesthesia can sometimes affect your coordination or sense of balance, and the stress of a surgical procedure may further impair your reactions.

Alcohol should be avoided for at least 24 hours after receiving prilocaine. Alcohol is a CNS depressant and can potentially worsen the sedative effects or dizziness associated with the anesthetic. Additionally, alcohol can interfere with the healing process of the procedure for which the anesthetic was given.

Prilocaine is not a medication that is 'taken' daily; therefore, there is no withdrawal syndrome. However, if you are using prilocaine/lidocaine topical cream for a chronic condition (which is off-label), do not stop or change the application frequency without consulting your doctor, as the underlying pain may return acutely.

> Important: Discuss all your medical conditions with your healthcare provider before starting Prilocaine.

There are few absolute contraindications for drug combinations with prilocaine, but the following should be avoided if possible:

• Other Methemoglobin-Inducing Agents: Drugs like sodium nitrite (used for cyanide poisoning) should never be used concurrently with prilocaine, as the combined effect on hemoglobin can be fatal.

Oxidizing Agents

The risk of methemoglobinemia is significantly increased when prilocaine is used with other drugs known to induce this condition. These include:

• Nitrates/Nitrites: Nitroglycerin, nitroprusside, and 'poppers' (amyl nitrite).
• Local Anesthetics: Benzocaine and lidocaine (additive risk).
• Antineoplastic Agents: Cyclophosphamide, flutamide, and rasburicase.
• Antibiotics: Sulfonamides (Bactrim), nitrofurantoin, and dapsone.
• Antimalarials: Chloroquine and primaquine.
• Anticonvulsants: Phenobarbital and phenytoin.

Antiarrhythmic Drugs

Patients taking Class I antiarrhythmic drugs (such as mexiletine or tocainide) should be monitored closely. Because prilocaine is also a sodium channel blocker, the toxic effects on the heart can be additive, leading to severe heart rhythm disturbances.

General Anesthetics

If prilocaine is used during a procedure where the patient is also receiving general anesthesia (like sevoflurane or propofol), the CNS-depressant effects may be additive. The anesthesiologist will adjust the doses of both agents accordingly.

Beta-Blockers and Cimetidine

These drugs can reduce blood flow to the liver or inhibit hepatic enzymes, potentially slowing the metabolism of prilocaine. This can lead to higher-than-expected blood levels of the anesthetic, increasing the risk of toxicity.

There are no specific food interactions with prilocaine. However, if the prilocaine was used for dental work, you must avoid eating until the numbness has completely worn off. This is to prevent accidental biting of the tongue, cheeks, or lips, which can cause significant injury without the patient feeling it.

• St. John's Wort: May theoretically induce liver enzymes, potentially altering how quickly prilocaine is cleared, though the clinical significance is likely low for a single dose.
• Vasoactive Supplements: Supplements that affect blood pressure (like ephedra or high doses of garlic/ginkgo) should be disclosed to the doctor, as they may interact with the epinephrine often found in prilocaine injections.

• Methemoglobin Test: Prilocaine will directly increase these levels.
• Liver Function Tests: Extremely high systemic levels could transiently affect liver enzyme readings, though this is not typical in clinical practice.
• False Pulse Oximetry: As mentioned, methemoglobin absorbs light at the same wavelengths as oxygenated and deoxygenated hemoglobin, leading to inaccurate 'oxygen saturation' readings on a standard finger clip.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking.

Prilocaine must NEVER be used in the following circumstances:

1. 1Hypersensitivity to Amide Anesthetics: If you have had a documented severe allergic reaction (anaphylaxis, severe hives) to prilocaine, lidocaine, bupivacaine, or mepivacaine, you must not receive prilocaine. The risk of cross-reactivity within the amide class is high.
2. 2Congenital or Idiopathic Methemoglobinemia: Patients born with a deficiency in the enzyme NADH-methemoglobin reductase cannot effectively convert methemoglobin back to functional hemoglobin. Giving prilocaine to these patients can cause rapid, life-threatening respiratory failure.
3. 3Severe Anemia: Patients with very low hemoglobin levels have no 'reserve' capacity. Even a small increase in methemoglobin can reduce their oxygen levels to dangerous points.

In these cases, the healthcare provider will perform a careful risk-benefit analysis:

• G6PD Deficiency: These patients are at a much higher risk of drug-induced hemolysis (breakdown of red blood cells) and methemoglobinemia.
• Severe Hepatic Disease: Because the liver is a site of metabolism, these patients are at risk for drug accumulation and CNS toxicity.
• Heart Block: Patients with second or third-degree heart block (without a pacemaker) should avoid prilocaine, as it can further slow electrical conduction in the heart.
• Severe Renal Impairment: Accumulation of the o-toluidine metabolite can occur, increasing the risk of blood disorders.

Patients allergic to 'ester' anesthetics (like procaine/Novocain) are generally not allergic to prilocaine. However, many local anesthetics contain a preservative called methylparaben. If a patient is allergic to parabens, they may react to many different types of anesthetics regardless of the drug class. Always specify if your allergy is to the 'caine' drug itself or to a preservative.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Prilocaine.

Prilocaine is classified as FDA Pregnancy Category B. This means that animal reproduction studies have failed to demonstrate a risk to the fetus, but there are no adequate and well-controlled studies in pregnant women.

• Labor and Delivery: Prilocaine is generally avoided for paracervical blocks in obstetrics because it can cross the placenta rapidly and has been associated with fetal methemoglobinemia and bradycardia.
• Clinical Decision: It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Most dentists and surgeons prefer lidocaine for pregnant patients if an amide anesthetic is required.

It is not known whether prilocaine is excreted in human milk. However, because many drugs are excreted in milk and because the half-life of prilocaine is relatively short (1.6 hours), the risk to a nursing infant is generally considered low. To be safe, some providers recommend 'pumping and discarding' milk for 4 to 6 hours after receiving the anesthetic. Always consult your pediatrician before breastfeeding after a procedure.

Prilocaine is approved for use in children, but the risk of methemoglobinemia is significantly higher in this population.

• Infants < 6 Months: Use is generally contraindicated because their metabolic pathways (specifically the enzyme cytochrome b5 reductase) are not fully developed, making them extremely susceptible to methemoglobinemia.
• Dosing: Must be strictly weight-based. Overdosing in children is a common cause of local anesthetic toxicity.

Patients over age 65 may have reduced liver and kidney function. Clinical studies suggest that the half-life of prilocaine may be prolonged in the elderly.

• Fall Risk: Because local anesthesia can affect proprioception (your sense of where your limbs are), elderly patients are at an increased risk for falls immediately following a procedure.
• Cardiovascular Reserve: Older patients are more likely to have underlying heart disease, making them more sensitive to the cardiac-depressant effects of prilocaine.

In patients with end-stage renal disease (ESRD), the clearance of prilocaine's metabolites is significantly reduced. While a single dental dose is usually safe, repeated doses or continuous infusions are avoided. Monitoring for signs of methemoglobinemia is essential in these patients.

For patients with a Child-Pugh score of B or C, the dose of prilocaine should be reduced by 25-50%. These patients should be observed for a longer period post-procedure for signs of delayed toxicity as the drug levels peak more slowly and stay elevated longer.

> Important: Special populations require individualized medical assessment.

Prilocaine is a local anesthetic of the amide type. Its primary molecular target is the voltage-gated sodium channel located on the internal surface of neuronal membranes. Prilocaine exists in an equilibrium between an uncharged lipid-soluble form and a charged water-soluble form. The uncharged form diffuses across the nerve membrane. Once inside, it becomes re-ionized and binds to the S6 segment of domain IV of the sodium channel alpha-subunit. This binding stabilizes the channel in the 'inactivated' state, preventing the rapid influx of sodium ions required for the depolarization of the nerve. This results in a 'conduction block,' preventing pain signals from traveling to the brain.

• Onset of Action: 1 to 5 minutes (for infiltration); 5 to 15 minutes (for nerve blocks).
• Duration: 1 to 2 hours (without epinephrine); 2 to 4 hours (with epinephrine).
• Potency: Prilocaine has a potency similar to lidocaine but is slightly less toxic to the central nervous system at equivalent doses.
• Vascular Effects: Unlike lidocaine, which is a vasodilator, prilocaine has minimal vasodilatory effects and can even cause mild vasoconstriction at certain concentrations.

| Parameter | Value |

|---|---|

| Bioavailability | 100% (Systemic Injection) |

| Protein Binding | 55% (Primarily Alpha-1-Acid Glycoprotein) |

| Half-life | 1.6 Hours (Terminal) |

| Tmax | 5-15 Minutes (Post-Injection) |

| Metabolism | Hepatic, Renal, and Pulmonary (Amidases) |

| Excretion | Renal (>95% as metabolites) |

• Molecular Formula: C13H20N2O
• Molecular Weight: 220.31 g/mol
• Solubility: Highly soluble in water (as the HCl salt); lipid-soluble as a free base.
• Structure: It consists of a lipophilic aromatic ring connected by an amide bond to a hydrophilic tertiary amine.

Prilocaine is classified as an Amide Local Anesthetic. It is grouped with lidocaine, bupivacaine, mepivacaine, and ropivacaine. It is distinct from the Ester Local Anesthetics (procaine, tetracaine, benzocaine) because it is metabolized by liver enzymes rather than plasma pseudocholinesterase.